“This study offers clues about clinical problems suffered in epilepsy that are often difficult to explain,” says Englot. “It’s an impetus to get treated sooner rather than let seizures continue to damage brain networks.” There is still a social stigma associated with seizures, and patients often fail to report episodes they’ve suffered, due to worries about losing their license to drive or their employment and insurance in some cases.
There are cases of epilepsy where drug treatments are not always effective — and a possible reason may be that they target the wrong areas. Englot’s work could be a step in the right direction for new pharmaceutical treatments, as well as new surgical procedures to stop recurring seizures — ones that may also be less invasive and more precise in the areas they target.
Traversing the Unknown
While our understanding of the brainstem’s components and their individual functions has become clearer in just the last few years — there’s one particular area within the medullary reticular formation that continues to elude neuroscientists. The nucleus gigantocellularis (NGC) is a relatively unexplored portion of the brainstem, but research published in Proceedings of the National Academy of Sciences suggests that it may play a role in cognition. So daunting and mysterious is the NGC that the study’s first author, Dr. Inna Tabansky, termed this region the brain’s “black box.”
Developing thoughts, coming up with the right word, and even the movement and senses rely on a mechanism known as “general arousal” — or GA — it’s that series of processes going on in your brain that wakes you up in the morning and keeps you alert before the first cup of coffee. More importantly, GA keeps us aware of ourselves and our environment — no matter how dark our room may be.
“It’s so fundamental that we don’t pay attention to it,” says Dr. Donald Pfaff, who heads the Laboratory of Neurobiology and Behavior at Rockefeller University: “And yet it’s so important that we should.”
Getting to the Root of the Problem
Tabansky, while experimenting with mice in the lab, came across a subtype of extremely large neurons within the NGC. So massive were these bundles of nerve that they linked essentially throughout the entire nervous system — in particular to the thalamus, where neurons are able to activate the entire cerebral cortex — the brain’s power house. The research team knew they were onto something important — they just weren’t quite sure where the roads led.
“If you just look at the morphology of NGC neurons, you know they’re important,” Pfaff says. “It’s just a question of what they’re important for. I think they’re essential for the initiation of any behavior.”
Tabansky and her team began their research by determining what genes the neurons expressed. It turns out, the NGC neurons code for an enzyme called endothelial nitric oxide synthase (eNOS), which is responsible for producing nitric oxide, which lowers blood pressure and accelerates the delivery of oxygenated blood to tissue. NGC neurons are the only neurons in the brain that produce this enzyme and the ones containing eNOS are also situated close to blood vessels.
Pfaff suggests that these neurons are so integral to carrying out normal functions of the central nervous system that they may have somehow evolved the ability to directly regulate their own supply of blood — sending eNOS into the nearby networks of blood vessels to deliver more when ready. While the researchers continue to find out the exact circumstances through which this may have come about, there was evidence to suggest that certain changes in the individual’s environment — such as a new smell — potential food or a predator, activated eNOS in the NGC neurons of lab mice.
“There is some low level of production when the animal is in a familiar setting,” says Tabansky, “which is what you expect as they maintain arousal. But it is vastly increased when the animal is adapting to a new environment.”
In the near future, Tabansky hopes that her team’s findings will be used to make further strides in the research of bipolar disorder. Genetic evidence suggests that neurons and their regulation of chemicals may also play a part in depression and suicidal feelings, though the exact mechanism remains unknown.
“By showing that this gene and its associated pathways have a particular role, at least in the rodent brain that relates to a fundamental function of the nervous system, is a hint about how this gene can cause psychiatric disease,” says Tabansky. “It’s very preliminary, and there is a lot more work to be done, but it potentially opens a new way to study how this gene can alter an individual’s psychology.”
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